The present series of studies have directly demonstrated an important in vivo antitumor role for large granular lymphocytes (LGL), the population of cells known to mediate natural killer (NK) and antibody-dependent cell mediated cytotoxicity (ADCC). The adoptive transfer of LGL into rats with depressed NK/ADCC activity was shown to restore in vitro tumor cell cytotoxicity, in vivo clearance of tumor cells from the lungs, and to inhibit the development of artificially induced lung metastases. These results provide the first direct evidence for an important in vivo antitumor role for LGL and suggest that the adoptive transfer of highly enriched LGL populations should be further considered as one potential immunotherapeutic regimen in cancer patients. Studies with the BRM, OK432, have shown this agent to augment NK activity and increase survival of tumor-bearing rats. In other experiments we have shown a number of differences in the organ, age and strain distribution between the NK and ADCC effector cell (K cell) populations. Additional experiments are now in progress to utilize these differences between NK and K cells to further investigate the in vivo relevance of these two natural immune systems. We are also investigating additional in vivo roles for NK cells in bone marrow transplanation and in the antiviral and antifungal immune responses.